Sessions of Prolonged Continuous TBS or High-frequency 10 Hz Stimulation to L-DLPFC for 3 Days Decreased Pain Sensitivity by Modulation of the Efficacy of Conditioned Pain Modulation

TITLE
Sessions of Prolonged Continuous Theta Burst Stimulation or High-frequency 10 Hz Stimulation to Left Dorsolateral Prefrontal Cortex for 3 Days Decreased Pain Sensitivity by Modulation of the Efficacy of Conditioned Pain Modulation

SOURCE
Journal of Pain. 20(12):1459-1469, 2019 12.

AUTHORS
De Martino E; Fernandes AM; Galhardoni R; De Oliveira Souza C; Ciampi De Andrade D; Graven-Nielsen T.

ABSTRACT
The 10 Hz repetitive transcranial magnetic stimulation (10 Hz-rTMS) to the left dorsolateral prefrontal cortex produces analgesia, probably by activating the pain modulation system. A newer rTMS paradigm, called theta burst stimulation (TBS), has been developed. Unlike 10 Hz-rTMS, prolonged continuous TBS (pcTBS) mimics endogenous theta rhythms, which can improve induction of synaptic long-term potentiation. Therefore, this study investigated whether pcTBS to the left dorsolateral prefrontal cortex reduced pain sensitivity more efficiently compared with 10 Hz-rTMS, the analgesic effects lasted beyond the stimulation period, and the reduced pain sensitivity was associated with increased efficacy of conditioned pain modulation (CPM) and/or intracortical excitability. Sixteen subjects participated in a randomized cross-over study with pcTBS and 10 Hz-rTMS. Pain thresholds to heat (HPT), cold, pressure (PPT), intracortical excitability assessment, and CPM with mechanical and heat supra-pain threshold test stimuli and the cold pressor test as conditioning were collected before (Baseline), 3 (Day3) and 4 days (Day4) after 3-day session of rTMS. HPTs and PPTs increased with 10 Hz-rTMS and pcTBS at Day3 and Day4 compared with Baseline (P=.007). Based on pooled data from pcTBS and 10 Hz-rTMS, the increased PPTs correlated with increased efficacy of CPM at Day3 (P=.008), while no correlations were found at Day4 or with the intracortical excitability.

PERSPECTIVE
Preliminary results of this comparative study did not show stronger pain sensitivity reduction by pcTBS compared with 10 Hz-rTMS to the L-DPFC. Both protocols maintained increased pain thresholds up to 24-hours after the last session, which were partially associated with modulation of CPM efficacy but not with the intracortical excitability changes.